Multiple Ascending Dose Study of TC-5619 in Healthy Elderly Subjects and Subjects With Alzheimer's Disease

Two-Part, Sequential Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TC-5619-238 in Elderly Subjects With and Without Alzheimer's Disease

This is a Phase 1 study to examine the safety, tolerability and pharmacokinetics of TC-5619 in elderly subjects with and without Alzheimer's disease. Group 1 includes elderly subjects with Alzheimer's disease to receive TC-5619 or placebo for 28 days to evaluate safety and tolerability. Group 2 includes healthy elderly subjects in a dose escalation design to receive TC-5619 or placebo for 10 days to evaluate safety, tolerability and pharmacokinetics.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: Placebo; Drug: TC-5619

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Long Beach, California, United States, 90806
      • Collaborative NeuroScience Network
    • San Francisco, California, United States, 94109
      • San Francisco Clinical Research Center
  • Florida
    • Hallandale Beach, Florida, United States, 33009
      • MD Clinical
    • Miami Springs, Florida, United States, 33166
      • Galiz Research
    • Miramar, Florida, United States, 333025
      • Comprehensive Phase One
    • Orlando, Florida, United States, 32806
      • Compass Research, LLC
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Atlanta Center For Clinical Research
  • New Jersey
    • Princeton, New Jersey, United States, 08540
      • Princeton Medical Institutes
  • Texas
    • Austin, Texas, United States, 78754
      • Community Clinical Research
  • Utah
    • Orem, Utah, United States, 84058
      • Aspen Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria (Groups 1 & 2):

• Normal body mass index (BMI)
• Non-smoking for a minimum of 3 months
• Subjects must be in reasonably good health, based on medical history, physical examination, vital signs, and ECG.

Group 1 Only:

• Subjects a Mini Mental State Examination score between 12-22, inclusive.
• Diagnosis of probable Alzheimer's Disease according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria
• Subjects must have a reliable caregiver.

Exclusion Criteria (Groups 1 & 2):

• Subjects with clinically significant heart disease, pulmonary disease, diabetes, neurologic or psychiatric disease (Group 1 subjects must have Alzheimer's Disease), or any other illness that could interfere with interpretation of study results.
• Subjects with a past or current history of seizures cannot participate.
• Current use of donepezil, rivastigmine or galantamine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Subjects will receive a placebo capsule orally once a day for 28 days (Group 1) or 10 days (Group 2).	Drug: Placebo; Group 1: matching placebo administered once daily for 28 days. Group 2: matching placebo administered once daily for 10 days.
Experimental: TC-5619; Subjects will receive a TC-5619 orally once a day for 28 days (Group 1) or 10 days (Group 2).	Drug: TC-5619; Group 1: 25 mg TC-5619 administered once daily for 28 days. Group 2: 50-150 mg TC-5619 administered once daily for 10 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	Number of participants with treatment-emergent adverse events	Group 1: screening, Days -14, Day -1, Days 1, 2, 3, 27-33; Group 2: Day -14, Day -1, Days 1 -14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic profiles	Plasma concentrations (pharmacokinetic profiles) of TC-5619-238 over time (Groups 1 & 2) and urine (Group 2) samples after multiple doses	Group 1: Days 1, 2, 28-32; Group 2: Day 1, 2, 4, 8, 10-14
Markers of inflammation in cerebrospinal fluid	Changes in markers of inflammation in cerebrospinal fluid (Group 1 only)	Group 1: Days 1, 2, 28-32; Group 2: Day 1, 2, 4, 8, 10-14
Markers of inflammation in plasma	Dose related changes in markers of inflammation in plasma over time (Groups 1 & 2)	Group 1: Days 1, 2, 28-32; Group 2: Day 1, 2, 4, 8, 10-14

Collaborators and Investigators

• Sponsor: Targacept Inc.
• Investigators: Principal Investigator: George Gerson, MD, Comprehensive Phase One

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: December 2, 2010
• First Submitted That Met QC Criteria: December 3, 2010
• First Posted (Estimate): December 6, 2010

Study Record Updates

• Last Update Posted (Estimate): September 4, 2013
• Last Update Submitted That Met QC Criteria: September 3, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: Alzheimer's Disease
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: TC-5619-238-CLP-003